Oxygenated derivatives of monoterpenes, such as nerol and citral, are of great importance to a number of industries. Although some processes for their commercial production are available, new and/or better synthetic routes are needed.
The application of organometallic chemistry to monoterpene transformation has been the subject of a number of studies. Early experiments are reported in McQuillin et al., J. Chem. Soc. Perkin Trans. I, pp. 809-815 (1974), and Dunne et al., J. Chem. Soc. (C). pp. 2196-2200, 2200-2203, and 2203-2206 (1970). In these studies, the authors prepared several allyl palladium complexes of terpene compounds, including those resulting from the reaction of palladium with myrcene. Cyclization of myrcene, however, was found to be a problem, and neither nerol nor citral resulted from the described processes.
Building on the earlier work of these authors, Takahashi et al., Journal of Organometallic Chemistry, Vol. 266, pp. 327-336 (1984) successfully prepared a mixture of citral and nerol utilizing a two-step method. First, myrcene was reacted with dichlorobis(acetonitrile)palladium in the solvent hexamethylphosphoric triamide (HMPA) or in the presence of a base such as Li.sub.2 CO.sub.3 using dimethylformamide (DMF) as solvent, to yield a non-cyclized palladium-myrcene complex. Although the reported yield of the palladium-myrcene complex in the HMPA process was relatively good, the complex formation in the Li.sub.2 CO.sub.3 /DMF process was somewhat low, approximately 33%. In the second step of the reported process, the complex was isolated, and then treated with base to yield terpene aldehydes and alcohols such as citral and nerol. One major drawback of these processes, however, is that they necessitate two steps, requiring isolation of the intermediate before further processing. Moreover, the product obtained using these methods is a mixture of both citral and nerol. Furthermore, these reactions have the additional disadvantage of a temperature limitation, since at high temperatures the solvents HMPA and DMF are decomposed by palladium species. See Bombieri et al., Inorganica Chimica Acta, Vol. 86, pp. 121-125 (1984); Fahey et al., Journal of Organic Chemistry, Vol. 39, pp. 3276-77 (1974). Finally, the use of HMPA in any process is undesirable, since HMPA is an extremely potent toxin, as well as a suspected carcinogen.
Nerol and citral are compounds of high significance to the flavor, fragrance and synthetic vitamin industries. Additional and/or better processes for their commercial production, particularly processes employing the readily available starting material myrcene, are needed. The present invention is directed to this important end.